Cargando…

Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers

OBJECTIVES: Two open-label, two-period, crossover studies in healthy volunteers were designed to determine the pharmacokinetic interactions between ticagrelor, a P2Y(12) receptor antagonist, and a moderate (diltiazem) and a strong (ketoconazole) cytochrome P450 (CYP) 3A inhibitor. METHODS: Seventeen...

Descripción completa

Detalles Bibliográficos
Autores principales: Teng, Renli, Butler, Kathleen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Maney Publishing 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937655/
https://www.ncbi.nlm.nih.gov/pubmed/27536435
http://dx.doi.org/10.3109/21556660.2013.785413
_version_ 1782441747411894272
author Teng, Renli
Butler, Kathleen
author_facet Teng, Renli
Butler, Kathleen
author_sort Teng, Renli
collection PubMed
description OBJECTIVES: Two open-label, two-period, crossover studies in healthy volunteers were designed to determine the pharmacokinetic interactions between ticagrelor, a P2Y(12) receptor antagonist, and a moderate (diltiazem) and a strong (ketoconazole) cytochrome P450 (CYP) 3A inhibitor. METHODS: Seventeen volunteers received diltiazem (240 mg once daily) for 14 days. In the second study, ketoconazole (n = 14) 200 mg twice daily was given for 10 days. A single oral 90-mg ticagrelor dose was administered on day 8 (diltiazem) or day 4 (ketoconazole). In each study, volunteers received a single 90-mg oral dose of ticagrelor before or after washout (≥14 days). Pharmacokinetic parameters for ticagrelor, AR-C124910XX (primary metabolite), diltiazem, and ketoconazole were assessed. RESULTS: Compared with ticagrelor alone, diltiazem co-administration significantly increased the mean maximum concentration (C(max)) and mean area under the plasma concentration–time curve (AUC) for ticagrelor by 69% and 174%, respectively. Diltiazem co-administration reduced C(max) by 38% but had no significant effect on AUC for AR-C124910XX. C(max) and AUC for ticagrelor were increased by 135% and 632%, respectively, by ketoconazole co-administration, whereas these parameters were reduced by 89% and 56%, respectively, for AR-C124910XX. Diltiazem and ketoconazole pharmacokinetic parameters were not significantly affected by the presence of ticagrelor. CONCLUSIONS: These results suggest that ticagrelor can be co-administered with moderate CYP3A inhibitors. However, co-administration of strong CYP3A inhibitors with ticagrelor is not recommended.
format Online
Article
Text
id pubmed-4937655
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Maney Publishing
record_format MEDLINE/PubMed
spelling pubmed-49376552016-08-17 Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers Teng, Renli Butler, Kathleen J Drug Assess Original Articles OBJECTIVES: Two open-label, two-period, crossover studies in healthy volunteers were designed to determine the pharmacokinetic interactions between ticagrelor, a P2Y(12) receptor antagonist, and a moderate (diltiazem) and a strong (ketoconazole) cytochrome P450 (CYP) 3A inhibitor. METHODS: Seventeen volunteers received diltiazem (240 mg once daily) for 14 days. In the second study, ketoconazole (n = 14) 200 mg twice daily was given for 10 days. A single oral 90-mg ticagrelor dose was administered on day 8 (diltiazem) or day 4 (ketoconazole). In each study, volunteers received a single 90-mg oral dose of ticagrelor before or after washout (≥14 days). Pharmacokinetic parameters for ticagrelor, AR-C124910XX (primary metabolite), diltiazem, and ketoconazole were assessed. RESULTS: Compared with ticagrelor alone, diltiazem co-administration significantly increased the mean maximum concentration (C(max)) and mean area under the plasma concentration–time curve (AUC) for ticagrelor by 69% and 174%, respectively. Diltiazem co-administration reduced C(max) by 38% but had no significant effect on AUC for AR-C124910XX. C(max) and AUC for ticagrelor were increased by 135% and 632%, respectively, by ketoconazole co-administration, whereas these parameters were reduced by 89% and 56%, respectively, for AR-C124910XX. Diltiazem and ketoconazole pharmacokinetic parameters were not significantly affected by the presence of ticagrelor. CONCLUSIONS: These results suggest that ticagrelor can be co-administered with moderate CYP3A inhibitors. However, co-administration of strong CYP3A inhibitors with ticagrelor is not recommended. Maney Publishing 2013-03-15 /pmc/articles/PMC4937655/ /pubmed/27536435 http://dx.doi.org/10.3109/21556660.2013.785413 Text en © 2013 The Author(s). Published by Taylor & Francis. 2013 http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Original Articles
Teng, Renli
Butler, Kathleen
Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers
title Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers
title_full Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers
title_fullStr Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers
title_full_unstemmed Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers
title_short Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers
title_sort effect of the cyp3a inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937655/
https://www.ncbi.nlm.nih.gov/pubmed/27536435
http://dx.doi.org/10.3109/21556660.2013.785413
work_keys_str_mv AT tengrenli effectofthecyp3ainhibitorsdiltiazemandketoconazoleonticagrelorpharmacokineticsinhealthyvolunteers
AT butlerkathleen effectofthecyp3ainhibitorsdiltiazemandketoconazoleonticagrelorpharmacokineticsinhealthyvolunteers